This phase II trial studies how well patients with stage I-IIIB rectal cancer respond to a short course of radiation therapy followed by chemotherapy. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Chemotherapy drugs, such as oxaliplatin, leucovorin, fluorouracil, and capecitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. A combination of radiation therapy and chemotherapy may prevent patients from needing surgery, could delay their need for surgery, or may mean that they need less drastic surgery and could potentially avoid a permanent ostomy (a surgically created connection between the intestine and the abdominal wall that allows for elimination of stool).
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03904043.
PRIMARY OBJECTIVE:
I. To determine the clinical complete response (cCR) response rate of patients with stage I-IIIB (cT1-3, N0-2a, M0) rectal cancer being treated with sequential short course radiotherapy followed by multi-drug chemotherapy.
SECONDARY OBJECTIVES:
I. To determine the 2 year progression free survival (PFS).
II. To determine the incidence of any grade >= 3 toxicity during treatment.
III. To determine the incidence of post chemoradiotherapy grade >= 3 toxicity at 1 year.
IV. To determine quality of anorectal function at 1 year using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire.
V. To determine the 1- and 2-year organ preservation rate.
EXPLORATORY OBJECTIVES:
I. To associate tumor microenvironment (including FAK expression) with cCR and other clinical outcomes.
II. To associate circulating tumor deoxyribonucleic acid (ctDNA) levels with cCR and other clinical outcomes.
OUTLINE:
Patients undergo 5 fractions of radiation therapy once daily (QD) over 5 days (Monday-Friday). Beginning 2-4 weeks, patients receive either FOLFOX regimen consisting of oxaliplatin intravenously (IV) over 2 hours, leucovorin IV over 2 hours, fluorouracil IV over 5-10 minutes followed by continuous infusion over 46 hours on day 1 or CAPOX regimen consisting of capecitabine orally (PO) twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment with FOLFOX repeats every 14 days for up to 8 cycles and treatment with CAPOX repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT), positron emission tomography (PET)/CT, PET/magnetic resonance imaging (MRI), and/or MRI throughout the trial. Patients also undergo blood sample collection during screening and on study and tissue biopsy during screening.
After completion of study treatment, patients are followed up every 3 months in year 1, every 3-4 months in year 2, and then every 4-6 months thereafter.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorMichael Richard Waters
